Human and rhesus macaque B-cell and serum antibody repertoires

人类和恒河猴 B 细胞和血清抗体库

• 批准号: 10229502
• 负责人: Michael Anthony Moody
• 金额: $ 56万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2023-04-06
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10229502
• 关键词: Adult; Affect; Antibodies; Antibody Binding Sites; Antibody Repertoire; Antigens; B cell repertoire; B-Lymphocytes; Binding Sites; Characteristics; Child; Development; Distant; Epitopes; Exposure to; Goals; Hemagglutinin; Human; Immune system; Immunity; Immunization; Immunize; Immunologic Memory; Individual; Infant; Infection; Influenza; Influenza vaccination; Life; Macaca mulatta; Memory; Methods; Mus; Outcome; Plasmablast; Protein Engineering; Public Health; Recommendation; Research; Sampling; Seasons; Serum; Specificity; Structure; Teenagers; Testing; Vaccination; Vaccines; Variant; design; global health; imprint; influenza infection; influenza virus strain; influenza virus vaccine; prevent; programs; receptor binding; recruit; response; trivalent influenza vaccine; vaccine trial

Summary Project 1, Moody The overall goal of the research program is to design immunogens that elicit a broadly neutralizing response Influenza remains a persistent global health threat requiring surveillance of circulating strains. The primary method of preventing influenza infection is vaccination, and in the last two decades, the recommendations for influenza vaccination have been expanded to include almost all people in the US. In a study of recipients of the 2008 trivalent influenza vaccine, we found that the response to influenza vaccination had subtype dominance: most of the responses in any particular individual were directed to a single component of the multivalent vaccine, and included responses to the hemagglutinin (HA) receptor binding site (RBS). We have now found that this dominant response derived from B cells descended from those elicited by the influenza strain circulating when these adults were infants, suggesting that an early influenza exposure may affect the outcome of later responses ("imprinting"). Investigating these observations has public health implications for the use of various influenza vaccines in infants and adults. Project 1 will test the hypotheses that (i) imprinting of the immune system by early infection with influenza results in subtype dominance in subsequent responses, but that (ii) early vaccination with multivalent vaccine in infants can prime the immune system to produce responses to multiple strains that persist across vaccine seasons and that can remain balanced even after an infection later in life, and (iii) that immunization with HAs designed to stimulate clonal lineages of RBS antibodies can modify an imprinted response. We will investigate these hypotheses in humans and rhesus macaques (RMs).

概括 项目1，穆迪 该研究计划的总体目标是设计能引起广泛中和反应的免疫原 流感仍然是一种持续的全球健康威胁，需要对流行毒株进行监测。初级 预防流感感染的方法是接种疫苗，在过去的二十年里，建议 流感疫苗接种范围已扩大到几乎所有美国人。在一项针对接受者的研究中 2008年三价流感疫苗，我们发现对流感疫苗接种的反应有亚型 支配性：任何特定个体的大多数反应都针对单一组成部分 多价疫苗，包括对血凝素（HA）受体结合位点（RBS）的反应。我们有 现在发现这种源自 B 细胞的显性反应源自流感引起的反应 这些成年人还是婴儿时流行的毒株，表明早期接触流感可能会影响 后来反应的结果（“印记”）。调查这些观察结果对公共卫生具有重要意义 在婴儿和成人中使用各种流感疫苗。项目 1 将测试以下假设：(i) 印记 早期感染流感会破坏免疫系统，导致随后的反应中亚型占主导地位， 但 (ii) 婴儿早期接种多价疫苗可以使免疫系统做好准备，产生 对多种菌株的反应在整个疫苗季节持续存在，并且即使在疫苗接种后也能保持平衡 晚年感染，以及 (iii) 旨在刺激 RBS 克隆谱系的 HA 免疫 抗体可以改变印记反应。我们将在人类和恒河猴中研究这些假设 猕猴（RM）。